Urinary incontinence is involuntary leakage of urine, and pathological urinary incontinence is a condition in which objective leakage, which is a social or hygienic problem, is observed. Stress urinary incontinence is leakage of urine upon a rise in abdominal pressure, such as during coughing, sneezing, laughing, or exercising, despite the absence of bladder contraction. Stress urinary incontinence has two main causes. One is hypermobility of the bladder neck and urethra. Descent of the bladder neck due to pelvic floor relaxation causes poor transmission of abdominal pressure to the urethra. Thus, upon a rise in abdominal pressure, only intravesical pressure is increased, resulting in leakage of urine. The other is intrinsic sphincter deficiency, leakage of urine upon a rise in abdominal pressure due to reduced sphincter function. Examples of the causes thereof include childbirth, obesity, aging, menopause, and pudendal nerve injury. Stress urinary incontinence is the most common type of urinary incontinence, and is reportedly observed in about 50% of female patients with urinary incontinence (Non-patent Literature 1). Urinary incontinence has significant adverse effects on women physically, mentally, and socially; inhibits participation in sports or social activities; and becomes a factor that decreases the quality of daily life (QOL). As a result, patients with stress urinary incontinence are made to suffer in their daily lives.
In recent years, duloxetine, a serotonin-noradrenaline reuptake inhibitor (SNRI), has been developed and used as a new therapeutic agent for stress urinary incontinence in Europe. However, since duloxetine also has an antidepressant action, and there are concerns about side effects such as suicide (Non-patent Literature 2), duloxetine has not been approved as a therapeutic agent for stress urinary incontinence in other countries, including the United States and Japan. Therefore, there is a demand for the development of drugs that are useful for stress urinary incontinence.
Patent Literature 1 to 3 describe benzilic acid ester compounds.